The present invention relates to a device and method for detecting Helicobacter Pylori in human subjects.
It has been known for some time that infection by Helicobacter pylori (H pylori) may increase the risk of a subject suffering from illnesses such as gastritis and duodenitis, and from peptic and duodenal ulcers. Detection of H pylori is therefore desirable to determine whether patients have, or have increased risk of having, such illnesses, and to enable appropriate treatment to be given.
H pylori produces ammonia and carbon dioxide by the action of a urease on urea in bodily fluids, and various tests have been proposed to detect H pylori by detecting the products of this reaction.
A test which is currently in use involves administering 13C-labelled urea to the subject and subsequently testing carbon dioxide in the subject""s breath for the presence of 13C. However, testing for 13C requires a sample to be sent away for laboratory testing, which is slow and relatively expensive.
Various methods are known for diagnosing the presence of H pylori in human subjects. In U.S. Pat. No. 4,947,861 it was proposed to detect the presence of ammonia in a subject""s breath following oral administration of urea. The method comprises collecting a sample of alveolar air at least ten minutes after administration of the urea, passing the air over an alkaline hygroscopic material to remove water vapour, and passing the dried alveolar air to a sensor which indicates the presence of ammonia. The sensor described is a glass tube filled with a granular material that changes colour as ammonia is passed through it. DE 299 02 593 U1 describes the use of an electronic xe2x80x9cnosexe2x80x9d for detecting infection by H pylori, and other conditions such as lactose intolerance, enzyme shortages, bacterial or viral infections. The electronic nose produces a fingerprint which is compared with a stored databank to produce a diagnosis. U.S. Pat. No. 5,719,052 describes a method and apparatus for collecting gas from a subject""s stomach by stimulating the subject""s vomiting reflex.
International Patent Application WO 97/3035 describes various chemical indicators which change colour in the presence of ammonia to provide a visible indicator of ammonia in a subject""s breath.
It is desirable to have a detection device and method for detecting H pylori which is non-invasive, speedy, and which can be used by a patient or other person without medical supervision.
According to a first aspect of the present invention there is provided a method for detecting the presence of Helicobacter pylori in the gastroenteral tract of a subject, the method comprising the steps of:
a) obtaining a volume of gas from the lungs and/or stomach of the subject;
b) dividing the said volume of gas into first and second substantially equal portions;
c) causing or permitting the first said portion of gas to come into intimate contact with a first electronic or electrochemical ammonia sensor connected to means for measuring the electrical resistance of the said first sensor;
d) causing or permitting the second said portion of gas to come into intimate contact with ammonia absorbing means and then into intimate contact with a second electronic or electrochemical ammonia sensor connected to means for measuring the electrical resistance of the said second sensor;
e) measuring the resistance of the first and second sensors when in contact with the said portions of gas;
f) comparing the said resistances of the sensors to produce a compared value; and
g) producing a visible output signal to indicate a positive or negative diagnosis of Helicobacter pylori infection according to whether or not the compared value exceeds a predetermined threshold value.
The method is non-invasive, and it can be speedy and easy for a patient or other subject to self-administer. It is not necessary to administer urea to the subject prior to carrying out the method.
An antacid (for example magnesium hydroxide) may be administered orally prior to testing. This will promote conversion of ammonium ions in the stomach to gaseous ammonia If the antacid is a carbonate or bicarbonate (for example sodium bicarbonate), it will also produce carbon dioxide to facilitate eructation.
A pair of similar sensors are provided, each in its own chamber. The gas is distributed substantially equally between the two chambers, but one chamber has an ammonia-absorbing barrier through which gas passes before coming into contact with the sensor. Electronics means compare the difference between or ratio of resistances of the two sensors and express the result as a visible output. The output could be numeric, but is preferably in the form of a signal corresponding to either a positive or a negative diagnosis. For example, a green light or a red light could be illuminated.
To further increase the sensitivity of the device, the gas could be passed through an alkaline desiccant (for example solid sodium hydroxide) in known manner, to remove water vapour (and some carbon dioxide) before the gas enters the chambers.
A preferred sensor comprises a film of polypyrrole, which is connected by electrodes to a suitable meter. Methods of making polypyrrole films suitable for use in the invention are described in GB 2 234 515 and EP 0 206 133. The film preferably has a thickness in the range 50 to 250 xcexcm.
According to another aspect of the present invention there is provided a detection device for measuring ammonia content in gas from a subject""s lungs and/or stomach, the device comprising:
a) a first chamber and a second chamber, each of which has an entrance opening for receiving the said gas, and each of which houses an electronic or electrochemical ammonia sensor connected to means for measuring the electrical resistance of the sensor;
b) the entrance openings of the chambers being connected to an inlet, the arrangement being such that incoming gas from the inlet will be divided into two substantially equal portions, each of which will pass through a corresponding entrance opening;
c) means for comparing the resistance of both sensors to produce a compared value;
d) means for producing a visible output signal according to whether the compared value exceeds a predetermined threshold value; and
e) wherein the second chamber is provided with means for absorbing ammonia, located between the entrance opening thereto and the sensor therein whereby at least some gas which enters the second chamber through the entrance opening will pass through the ammonia-absorbing means.
Although the term xe2x80x9cammonia-absorbing meansxe2x80x9d is used herein for convenience, it will be understood that this term includes any means which remove ammonia from the gas. Thus, the term includes amonia adsorbents and materials which chemically combine with ammonia.
A preferred ammonia sensor comprises a film of polypyrrole, connected by electrodes to a suitable meter.
In a preferred embodiment, each chamber is provided with an exit vent to facilitate the passage of gas therethrough.
To reduce the volume of xe2x80x9cdead spacexe2x80x9d in the chambers, they may optionally be constructed to be expandable, for example by having elastic walls, by being of telescopic construction, or by having a movable plunger, like a syringe. By reducing dead space, and therefore dilution of the gas portions, the sensitivity of the method can be increased.